Prevention of Transplant Atherosclerosis With Everolimus and Anti-cytomegalovirus Therapy

Phase 3

• Conditions: Heart Transplantation; Cytomegalovirus Infection; Cardiac Allograft Vasculopathy
• Interventions: Drug: Prophylaxis with valganciclovir plus mycophenolate; Drug: Pre-emptive strategy with valganciclovir plus everolimus; Drug: Prophylaxis with valganciclovir plus everolimus; Drug: Pre-emptive mycophenolate

• Registration Number: NCT00966836
• Lead Sponsor: University of Bologna

Brief Summary

Cardiac allograft vasculopathy (CAV) is the major cause of long-term graft failure in heart transplant recipients. Although several immune-mediated and metabolic risk factors have been implicated in the pathogenesis of CAV, no effective therapy is currently available to treat established CAV and prevent its adverse outcomes. Therefore, the main clinical strategy is based on prevention and treatment of factors known to trigger its development. Although the mechanism is vague, cytomegalovirus (CMV) infection is believed to play a key role in CAV progression.

Two strategies involving administration of specific anti-CMV agents are recommended for prevention of CMV infection/disease: universal prophylaxis and preemptive therapy. The pros and cons of the two strategies are still debated, in the absence of randomized studies addressing graft-related outcomes and viral mechanisms of graft damage, and without any clear evidence of superiority of either approach.

The investigators conceived this randomized prospective project to compare the effect of preemptive anti-CMV strategy with universal anti-CMV prophylaxis on CMV infection and on one-year increase in coronary intimal thickening. Patients will be additionally randomized to receive either mycophenolate mofetil or everolimus, in light of the possible anti-CMV properties of everolimus.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-04
• Status Verified: 2009-08
• Study First Submitted: 2009-08-26
• Study First Submitted QC: 2009-08-26
• Last Update Submitted: 2009-08-26
• Study First Posted: 2009-08-27
• Last Update Posted: 2009-08-27
• Primary Completion: 2012-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Age ≥ 18y
• Heart or heart-kidney combined transplant
• Positive CMV serology at the time of transplant
• Glomerular filtration rate ≥ 20 ml/min/1.73m2 with MDRD at randomization.
• Written informed consent

Exclusion Criteria

• Panel Reactive Antibody ≥50%
• Less than 1000/mmc neutrophils at the time of randomization
• Less than 30,000/mmc platelets at the time of randomization
• Clinical significant infection in the 2 weeks prior to transplant
• Glomerular filtration rate < 20 ml/min/1.73m2 estimated with MDRD formula at the time of randomization or hemodialysis treatment
• Intolerance towards valganciclovir, everolimus, mycophenolate or cyc-losporine
• Known contraindication to statin use
• Negative CMV serology at the time of transplant
• HIV positive testing
• Severe comorbidities that, based on investigator's judgment, contraindicate study drugs or procedures
• Potentially childbearing women who refuse to use contraceptives
• Participation to an interventional study in the 2 preceding weeks
• Unwillingness or inability to follow study procedure and to sign written in-formed consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prophylaxis mycophenolate	Prophylaxis with valganciclovir plus mycophenolate	-
Pre-emptive everolimus	Pre-emptive strategy with valganciclovir plus everolimus	-
Prophylaxis Everolimus	Prophylaxis with valganciclovir plus everolimus	-
Pre-emptive mycophenolate	Pre-emptive mycophenolate	-

Primary Outcome Measures

Name	Time	Method
Change in maximal intimal thickness	one year

Secondary Outcome Measures

Name	Time	Method
CMV infection	one year

Trial Locations

Locations (1)

Azienda Ospedaliero-Universitaria S Orsola Malpighi; 🇮🇹 Bologna, Italy